It is known that some biologically inactive steroids present in blood are converted to potent hormones in peripheral tissues. This conversion can take place in tissues responsive to the action of the active form of the circulating steroid. In other instances a steroid believed to exert one biological function (e.g., testosterone) is converted, in extraglandular tissues, to a hormone with a totally different function (e.g.,17 Beta-estradiol). Little is known of the tissue site(s) in which extraglandular hormone transformations are accomplished. At the present time there are suggestions to indicate that the human lung may be a site of peripheral activation of blood-borne steroids. No systematic studies have been undertaken to define the extent and role of these metabolic processes in this organ. We propose to investigate and define the role of the human lung in the metabolism of blood-borne steroid hormones. Specifically, we propose: 1) to investigate the metabolic capacity of human lung tissue to convert androgens to estrogens, and to study the metabolism of glucocorticosteroids (cortisol), mineralocorticosteroids (desoxycorticosterone), estrogens (estrone, 17 Beta-estradiol and estriol), and steroid sulfates (dehydroisoandrosterone sulfate and estrone sulfate) by slices of human lung tissues; 2) to study the role of specific human pneumocytes, viz., pulmonary endothelial cells, alveolar macrophages, alveolar type II epithelial cells (cell line A-549) and lung fibroblasts (cell line WI 38) in the metabolism of the above mentioned steroids; 3) to evaluate specific steroid receptors in human lung tissue and in isolated pneumocytes; 4) to study steroid dynamics in human lung tissue and pneumocytes at near-physiologic concentrations of steroid substrates, using the superfusion technique. The findings of such studies will provide definitive information on the steroid metabolizing capacilities of human lung tissue as well as those of the available pneumocytes, and also will define the type of steroid receptors present in this tissue.